Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

English version České info

Despite the higher prevalence of type 2 diabetes (T2D) in African Americans than in Europeans, recent genome-wide association studies (GWAS) were examined primarily in individuals of European ancestry. In this study, we performed meta-analysis of 17 GWAS in 8,284 cases and 15,543 controls to explore the genetic architecture of T2D in African Americans. Following replication in additional 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry, we identified two novel and three previous reported T2D loci reaching genome-wide significance. We also examined 158 loci previously reported to be associated with T2D or regulating glucose homeostasis. While 56% of these loci were shared between African Americans and the other populations, the strongest associations in African Americans are often found in nearby single nucleotide polymorphisms (SNPs) instead of the original SNPs reported in other populations due to differential genetic architecture across populations. Our results highlight the importance of performing genetic studies in non-European populations to fine map the causal genetic variants.

Vyšlo v časopise: Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004517
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004517

Souhrn

Zdroje

1. Centers for Disease Control and Prevention (2011) National diabetes fact sheet: National estimates and general information on diabetes and prediabetes in the United States. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention.

2. McCarthyMI (2010) Genomics, type 2 diabetes, and obesity. N Engl J Med 363 : 2339–2350.

3. VoightBF, ScottLJ, SteinthorsdottirV, MorrisAP, DinaC, et al. (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 42 : 579–589.

4. KoonerJS, SaleheenD, SimX, SehmiJ, ZhangW, et al. (2011) Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nat Genet 984–989.

5. ChoYS, ChenCH, HuC, LongJ, Hee OngRT, et al. (2011) Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in East Asians. Nat Genet 44 : 67–72.

6. PalmerND, McDonoughCW, HicksPJ, RohBH, WingMR, et al. (2012) A genome-wide association search for type 2 diabetes genes in African Americans. PLoS ONE 7: e29202.

7. MorrisAP, VoightBF, TeslovichTM, FerreiraT, SegreAV, et al. (2012) Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 44 : 981–990.

8. DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium, Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) Consortium (2014) Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat Genet 46 : 234–244.

9. RotimiC, CooperR, CaoG, SundarumC, McGeeD (1994) Familial aggregation of cardiovascular diseases in African-American pedigrees. Genet Epidemiol 11 : 397–407.

10. AbecasisGR, AutonA, BrooksLD, DePristoMA, DurbinRM, et al. (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491 : 56–65.

11. DevlinB, RoederK (1999) Genomic control for association studies. Biometrics 55 : 997–1004.

12. WillerCJ, LiY, AbecasisGR (2010) METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26 : 2190–2191.

13. HaraK, FujitaH, JohnsonTA, YamauchiT, YasudaK, et al. (2014) Genome-wide association study identifies three novel loci for type 2 diabetes. Hum Mol Genet 23 : 239–246.

14. Genomes Project Consortium (2010) A map of human genome variation from population-scale sequencing. Nature 467 : 1061–1073.

15. UnokiH, TakahashiA, KawaguchiT, HaraK, HorikoshiM, et al. (2008) SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet 40 : 1098–1102.

16. YasudaK, MiyakeK, HorikawaY, HaraK, OsawaH, et al. (2008) Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet 40 : 1092–1097.

17. TakeuchiF, SerizawaM, YamamotoK, FujisawaT, NakashimaE, et al. (2009) Confirmation of multiple risk loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population. Diabetes 58 : 1690–1699.

18. ParraEJ, BelowJE, KrithikaS, ValladaresA, BartaJL, et al. (2011) Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas. Diabetologia 54 : 2038–2046.

19. CuiB, ZhuX, XuM, GuoT, ZhuD, et al. (2011) A genome-wide association study confirms previously reported loci for type 2 diabetes in Han Chinese. PLoS ONE 6: e22353.

20. TsaiFJ, YangCF, ChenCC, ChuangLM, LuCH, et al. (2010) A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet 6: e1000847.

21. StoyJ, SteinerDF, ParkSY, YeH, PhilipsonLH, et al. (2010) Clinical and molecular genetics of neonatal diabetes due to mutations in the insulin gene. Rev Endocr Metab Disord 11 : 205–215.

22. PetrikJ, PellJM, AranyE, McDonaldTJ, DeanWL, et al. (1999) Overexpression of insulin-like growth factor-II in transgenic mice is associated with pancreatic islet cell hyperplasia. Endocrinology 140 : 2353–2363.

23. CalderariS, GangnerauMN, ThibaultM, MeileMJ, KassisN, et al. (2007) Defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly in the Goto-Kakizaki rat model of type 2 diabetes. Diabetologia 50 : 1463–1471.

24. RamosE, ChenG, ShrinerD, DoumateyA, GerryNP, et al. (2011) Replication of genome-wide association studies (GWAS) loci for fasting plasma glucose in African-Americans. Diabetologia 54 : 783–788.

25. FraylingTM, TimpsonNJ, WeedonMN, ZegginiE, FreathyRM, et al. (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316 : 889–894.

26. HertelJK, JohanssonS, SonestedtE, JonssonA, LieRT, et al. (2011) FTO, type 2 diabetes, and weight gain throughout adult life: a meta-analysis of 41,504 subjects from the Scandinavian HUNT, MDC, and MPP studies. Diabetes 60 : 1637–1644.

27. LiH, KilpelainenTO, LiuC, ZhuJ, LiuY, et al. (2012) Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians. Diabetologia 55 : 981–995.

28. BinhTQ, PhuongPT, NhungBT, ThoangDD, LienHT, et al. (2013) Association of the common FTO-rs9939609 polymorphism with type 2 diabetes, independent of obesity-related traits in Vietnamese population. Gene 513 : 31–35.

29. DunhamI, KundajeA, AldredSF, CollinsPJ, DavisCA, et al. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489 : 57–74.

30. WardLD, KellisM (2012) HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res 40: D930–934.

31. BellAC, FelsenfeldG (2000) Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405 : 482–485.

32. OshelKM, KnightJB, CaoKT, ThaiMV, OlsonAL (2000) Identification of a 30-base pair regulatory element and novel DNA binding protein that regulates the human GLUT4 promoter in transgenic mice. J Biol Chem 275 : 23666–23673.

33. Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447 : 661–678.

34. BarrettJC, ClaytonDG, ConcannonP, AkolkarB, CooperJD, et al. (2009) Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 41 : 703–707.

35. PlagnolV, HowsonJM, SmythDJ, WalkerN, HaflerJP, et al. (2011) Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. PLoS Genet 7: e1002216.

36. DabeleaD, PihokerC, TaltonJW, D'AgostinoRBJr, FujimotoW, et al. (2011) Etiological approach to characterization of diabetes type: the SEARCH for Diabetes in Youth Study. Diabetes Care 34 : 1628–1633.

37. Barinas-MitchellE, PietropaoloS, ZhangYJ, HendersonT, TruccoM, et al. (2004) Islet cell autoimmunity in a triethnic adult population of the Third National Health and Nutrition Examination Survey. Diabetes 53 : 1293–1302.

38. HakonarsonH, GrantSF, BradfieldJP, MarchandL, KimCE, et al. (2007) A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature 448 : 591–594.

39. ErlichH, ValdesAM, NobleJ, CarlsonJA, VarneyM, et al. (2008) HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes 57 : 1084–1092.

40. HowsonJM, WalkerNM, ClaytonD, ToddJA (2009) Confirmation of HLA class II independent type 1 diabetes associations in the major histocompatibility complex including HLA-B and HLA-A. Diabetes Obes Metab 11 Suppl 1 : 31–45.

41. EikeMC, BeckerT, HumphreysK, OlssonM, LieBA (2009) Conditional analyses on the T1DGC MHC dataset: novel associations with type 1 diabetes around HLA-G and confirmation of HLA-B. Genes Immun 10 : 56–67.

42. HowsonJM, RoyMS, ZeitelsL, StevensH, ToddJA (2013) HLA class II gene associations in African American Type 1 diabetes reveal a protective HLA-DRB1*03 haplotype. Diabet Med 30 : 710–716.

43. NobleJA, JohnsonJ, LaneJA, ValdesAM (2013) HLA class II genotyping of African American type 1 diabetes patients reveals associations unique to African haplotypes. Diabetes 62 : 3292–3299.

44. OdegaardJI, ChawlaA (2012) Connecting type 1 and type 2 diabetes through innate immunity. Cold Spring Harb Perspect Med 2: a007724.

45. RichSS, FrenchLR, SprafkaJM, ClementsJP, GoetzFC (1993) HLA-associated susceptibility to type 2 (non-insulin-dependent) diabetes mellitus: the Wadena City Health Study. Diabetologia 36 : 234–238.

46. CervinC, LyssenkoV, BakhtadzeE, LindholmE, NilssonP, et al. (2008) Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes. Diabetes 57 : 1433–1437.

47. RajSM, HowsonJM, WalkerNM, CooperJD, SmythDJ, et al. (2009) No association of multiple type 2 diabetes loci with type 1 diabetes. Diabetologia 52 : 2109–2116.

48. LukacsK, HosszufalusiN, DinyaE, BakacsM, MadacsyL, et al. (2012) The type 2 diabetes-associated variant in TCF7L2 is associated with latent autoimmune diabetes in adult Europeans and the gene effect is modified by obesity: a meta-analysis and an individual study. Diabetologia 55 : 689–693.

49. LiY, WillerCJ, DingJ, ScheetP, AbecasisGR (2010) MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol 34 : 816–834.

50. HowieBN, DonnellyP, MarchiniJ (2009) A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet 5: e1000529.

51. BrowningSR, BrowningBL (2007) Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. Am J Hum Genet 81 : 1084–1097.

52. ChenMH, YangQ (2010) GWAF: an R package for genome-wide association analyses with family data. Bioinformatics 26 : 580–581.

53. AlmasyL, BlangeroJ (1998) Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 62 : 1198–1211.

54. SkolAD, ScottLJ, AbecasisGR, BoehnkeM (2006) Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet 38 : 209–213.

55. MagiR, MorrisAP (2010) GWAMA: software for genome-wide association meta-analysis. BMC Bioinformatics 11 : 288.

56. LinS, ChakravartiA, CutlerDJ (2004) Exhaustive allelic transmission disequilibrium tests as a new approach to genome-wide association studies. Nat Genet 36 : 1181–1188.

57. WrayNR, YangJ, GoddardME, VisscherPM (2010) The genetic interpretation of area under the ROC curve in genomic profiling. PLoS Genet 6: e1000864.

58. BarrettJC, FryB, MallerJ, DalyMJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21 : 263–265.

59. PurcellS, ChernySS, ShamPC (2003) Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19 : 149–150.

60. NicaAC, PartsL, GlassD, NisbetJ, BarrettA, et al. (2011) The architecture of gene regulatory variation across multiple human tissues: the MuTHER study. PLoS Genet 7: e1002003.

61. AulchenkoYS, RipkeS, IsaacsA, van DuijnCM (2007) GenABEL: an R library for genome-wide association analysis. Bioinformatics 23 : 1294–1296.

62. AulchenkoYS, StruchalinMV, van DuijnCM (2010) ProbABEL package for genome-wide association analysis of imputed data. BMC Bioinformatics 11 : 134.

63. StrangerBE, ForrestMS, DunningM, IngleCE, BeazleyC, et al. (2007) Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315 : 848–853.

64. BoyleAP, HongEL, HariharanM, ChengY, SchaubMA, et al. (2012) Annotation of functional variation in personal genomes using RegulomeDB. Genome Res 22 : 1790–1797.

65. Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447 : 661–678.